A recent clinical trial demonstrated a beneficial effect of heparin administration in the luteal phase on implantation rate as well as the live birth rate in women with repeated implantation failure. However, the precise effects of heparin on decidualization process remain uncertain. Addition of heparin at various concentrations to decidualized HESCs caused a dose-dependent increase of PRL secretion. Decidualized HESCs treated with heparin dose-dependently prevented the cell death rate induced by oxidative stress. Heparin augmented both FOXO1 and SOD2 protein expression. These results demonstrate that heparin-treated decidualized HESCs acquired resistance to oxidative stress by induced expression of FOXO1 and SOD2, suggesting that heparin may improve the uterine environment for successful implantation.